Abstract

MicroRNAs (miRNAs) are endogenous non-coding short single-stranded RNAs that are evolutionarily conserved and believed to play a role in controlling a variety of biological processes. The roles of miRNAs in insulin resistance and liver steatosis, however, are largely unknown. The objective of this study was to evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver steatosis. In our current study, we observed that overexpression of miR-130a-3p increases insulin signaling in both HepG2 cells and primary mouse hepatocytes and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has no effect in the regulation of insulin signaling. Consistently, whole body and hepatic insulin sensitivity is improved in mice injected with adenoviruses that over-express miR-130a-3p. Furthermore, we provided evidence showing that growth factor receptor-bound protein 10 is required for miR-130a-3p-regulated insulin sensitivity. On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice. This study identifies a novel function for hepatic miR-130a-3p in the regulation of insulin sensitivity and liver steatosis.